Int J Clin and Biomed Res. 2017;3(1):13-17.

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Research article
ELECTROPHYSIOLOGICAL CHANGES IN LATENCY IN DIABETIC RETINOPATHY:
AN OBSERVATIONAL STUDY
AMRUTA VIJAY MORE1*, APARNA GHODAKE2 , CHINTAN SHAH3 , AISHWARYA CHHABRA 4 , JIGNESH GOSAI 5 .

AUTHOR DETAILS ABSTRACT

Received: 26 th Dec 2016
Revised: 30 th Dec 2016
Accepted: 05 th Jan 20167
Author details:
1,2 Resident doctor,
3 MBBS, DO,
4 MS Ophthalmology,
5 MS Ophthalmology and Assistant
Professor, M & J Institute of
Ophthalmology, Civil hospital,
Ahmedabad 380016.
*Corresponding author:
Dr. Amruta Vijay More
Email: dramrutavmore@gmail.com
Purpose: Multifocal ERG is a useful indicator of diabetic retinopathy. The significant
delay in local responses provides a chance for the detection and understanding of the
various stages of diabetic retinopathy. Materials and Methods: This is a cross sectional
study conducted in ERG clinic at M&J Western regional institute of ophthalmology,
Ahmedabad from January 2013 to September 2015 who were more than 35yrs of age.
Results: In our study, we studied 45 eyes of diabetic patients and 20 eyes of normal
subjects. In our study the mean values of the various parameters was calculated in the
control group with N1, P1 and N2 latency being 14.09ms. 29,76ms and 45.55ms
respectively. The N1, P1 and N2 amplitude was found to be 31.52nV, 73.61nV and
90.38nV respectively. The maximum delay in N1, P1 and N2 latency was seen to be
3.24ms, 7.11ms and 8.40ms respectively from the normal value. We also found a
decrease in amplitude of the ERG waveform with N1, P1 and N2 amplitude being
20.98nV,61.48nV and 76.4nV respectively from the normal value. Also it is helpful in
cases with clinically significant macular edema where responses are remarkably dela yed
suggesting local retinal dysfunction and macular pathology. It provides us information
regarding the condition of the macula and some ideas about the extent of ischemia
affecting this area. Conclusion: In conclusion, we can say that the delayed responses
obtained indicate abnormal retinal function corresponding to local discrete retinal
lesions. It provides a very sensitive and objective assessment of the local retinal
condition in various stages of diabetic retinopathy.

KEYWORDS: Diabetes mellitus, Diabetic retinopathy, Multifocal electroretinogram.

INTRODUCTION resulting in basement membrane thickening and loss of

pericytes [3].
Diabetes Mellitus (DM) is a heterogenous group of metabolic
Retinopathy is the most common microvascular complication
disorder characterized by chronic hyperglycemia with
of diabetes, and it remains a major cause of new onset
disturbance of carbohydrate, fat and protein metabolism
blindness in age group of 20-74 years of patients worldwide.
resulting from defect in insulin secretion, insulin action or
Vascular lesions in the early stages of diabetic retinopathy
both[1]. The worldwide prevalence of DM has risen
are characterized by the presence of capillary
dramatically over the past two decades, from an estimated
microaneurysms, pericyte deficient capillaries, and
30 million cases in 1985 to 285 million in 2010 . Chronic
obliterated and degenerated capillaries. Proliferative diabetic
diabetes results in the development of tissue complications,
retinopathy is the more advanced form of the disease, when
mainly microvascular (retinopathy, nephropathy and
circulation problems cause the retina to become hypoxic. As
neuropathy) and macrovascular disease (atherosclerosis) [2].
a result, new fragile blood vessels can begin to grow in the
Microangiopathy is characterized by progressive occlusion of
retina and into the vitreous.
the capillary lumen with subsequent impaired tissue
Electroretinogram (ERG)[4] is the neurophysiological test used
perfusion, increased vascular permeability and increased
in order to measure electric changes that happen in the
production of extracellular material by perivascular cells,
retina after a light stimulus. Full-field electroretinogram

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 Int J Clin and Biomed Res. 2017;3(1): 13-17.
(ERG) has been used as an objective tool to detect alterations
of retinal function during the early stages of diabetes, to
predict the progression of diabetic retinopathy and to
monitor the treatment effects. The sensitivity of the full -field
ERG is limited, precisely because it reflects the activity of the
entire retina. Even advanced disease, if confined to small,
discrete patches, can remain undetected by the full -field
ERG. (e.g., focal edema and capillary non perfusion).
In contrast, the Multifocal electroretinogram (mfERG)
developed by Sutter [5] and Tran and Bearse[6] and Sutter
enables assessment of up to hundreds of distinct retinal
areas, posterior region around macula within approximately
8 minutes per eye.
Aims & Objectives
Retinopathy is one of the most important complications of
chronic diabetes. It increases gradually and sometimes seen
at a very late stage when visual symptoms become obvious
or when fundus findings are noted.
Through this study, we would like to assess:
1. The effect of diabetes on multifocal ERG findings.
2. The effect of different stages of diabetic retinopathy on
multifocal ERG findings.
MATERIALS & METHODS
Study Design/Place of study: It was a cross sectional study
Study location: The study was conducted at M & J Western
Regional institute of Ophthalmology, Ahmedabad from
January 2013 to September 2015.
Inclusion criteria: Patients who had mild to moderate non
proliferative diabetic retinopathy (NPDR) with clinically
significant macular edema (CSME) age between 35-65 years
of both sexes.
Exclusion criteria: Following subjects were excluded from the
study: History of glaucoma, addiction of alcohol, addiction of
smoking, retinal detachment due to any reason, Visual acuity
<6/60 and mentally challenged patients
Sample Size:
On the basis of clinical evaluation and fundus examination,
the subjects were divided into 3 groups -
GROUP 1: 20 eyes of patients who did not have diabetes
were taken as control.
GROUP 2: 25 eyes of patients who had mild to moderate non
proliferative diabetic retinopathy (NPDR) with clinically
significant macular edema (CSME).
GROUP 3: 20 eyes of patients who had severe NPDR with
CSME.
Method of data collection:
The data was collected by means of a personal interview by
history taking, physical examination and performing the
tests. The procedure of examination performed was
explained to all the cases and written consent was taken
prior to examination.
Amruta Vijay More et al.,
Page 14
Visual acuity: Taken on Snellens chart[7,8].
Slit lamp examination: It was done to examine the anterior
segment as well as fundus using 90 D lense.
Fundus examination: It was done using slit lamp
biomicroscopy,direct and indirect ophthalmoscopy.
Fundus fluorescein angiography: It was also done to
completely evaluate the vascular system of retina.
Multifocal electroretinogram: It was done in each patients
under same condition using ISCEV[9] Standards.
Classifications and cut-offs parameters
HBA1C: Patients with HbA1C >6.5 %( 48 mmol/mol) were
taken as diabetics.
Fasting and Post Prandial Blood Sugar: Diabetics: Subjects
with fasting blood sugar >126mg/d1 or >7.0 mmol/1 and post
prandial blood sugar >200 mg/dl or >11.1 mmol /1 and
known cases of diabetes irrespective of their current
treatment status and glycemic control status. All others were
considered as non-diabetics.
Visual Acuity: Subjects with Visual Acuity 6/6 to 6/12 were
taken in the control group. Visual acuity more than 6/60
were taken in diabetic group.
Statistical analysis: The data was analyzed using Microsoft
excel by applying unpaired t-test for quantitative data and
using Epi Info 7 version 7.0.8.3 by chi- square test for
qualitative data . Correlation coefficients and Odds ratio were
calculated for the different variables. Significance level was
taken as p < 0.05.
RESULTS
Table 1. Age wise distribution of the subjects
AGE GROUP (Years) GROUP 1 GROUP 2 GROUP 3
35-45 2 0 1
45-55 8 11 6
55-65 10 14 13
Table 2. Sex wise distribution of subjects
SEX GROUP 1 GROUP 2 GROUP 3
MALE 12 10 14
FEMALE 8 15 6
Figure 1 shows higher values of FBS, PPBS and HbA1C in the
diabetic group as compared to the control group and the
difference was found to be statistically significant with the P
value being less than 0.0001 for all the parameters. It shows
a linear increase in the mean values of FBS, PPBS and HbA1C
from group 1 to group 3 as the severity of the disease
increases.
Comparison of latency and amplitude of erg in 3 groups : A
mean value of the local responses in multifocal ERG was
calculated in terms of N1, P1, N2 latencies and amplitudes of
all the subjects and was analyzed.
 Int J Clin and Biomed Res. 2017;3(1): 13-17.

250 229.15
Above figures (Figure 3 & 4) show an increase in N1 latency
of 3.24ms and a decrease in N1 amplitude of 20.98nV from
196.64
200 group 1 to group 3 suggesting that the latency increases and
the amplitude increases as the severity of the disease
150 139.55 increases.
FBS mg/dl
123.04
114 P1 LATENCY
PPBS mg/dl
100 40
74.05 HbA1C gm%
35
50 30
7.2 7.27

in milliseconds
4.56 25
0
20
Group1 Group2 Group3
15
Figure 1. COMPARISON OF FBS(mg/dl) , PPBS (mg/dl) and 10
HbA1C (gm%) in 3 groups
5

0
P1 IMPLICIT TIME GROUP 1 GROUP 2 GROUP 3
P1 LATENCY 29.76 34.32 36.87
40
35
Figure 5. Comparison of p1 latency in 3 groups.
30
in milliseconds

25
20
P1 AMPLITUDE
15
10 80
5 70
0 60
GROUP1 GROUP2 GROUP2 50
P1 IMPLICIT TIME 22.63 28.59 34.11 40
in nV

30
Figure 2. Comparison of p1 implicit time in 3 groups 20
10

Figure 2 shows an increase in the P1 implicit time from 0

GROUP 1 GROUP 2 GROUP 3
22.63ms in group 1 to 28.59ms in group 2. A further P1 AMPLITUDE 73.61 31.65 12.13

increment was noted in group 3 where it is 34.11ms.

Figure 6. Comparison of p1 amplitude in 3 groups

N1 LATENCY The figures above (Figure 5 & 6) suggest that the P1 latency
20
increases with the difference of 4.56 ms between group 1
in milliseconds

and group 2 and difference of 2.55ms between group 2 and

15
group 3. The P1 amplitude decreases significantly with a
10
difference of 61.48 between group 1 and group 3.
5

0
GROUP 1 GROUP 2 GROUP 3 N2 LATENCY
N1 LATENCY 14.09 15.81 17.33
56
in milliseconds

54
Figure 3. Comparison of n1 latency in 3 groups.
52
50
48
35 46
30 44
25 42
20 40
in nV

GROUP 1 GROUP 2 GROUP 3

15
10 N2 LATENCY 45.55 50.49 53.95
5
0 Figure 7. Comparison of n2 latency in 3 groups
GROUP 1 GROUP 2 GROUP 3
N1 AMPLITUDE 31.52 16.27 10.54 The Figure 7 & 8 show an increase in the N2 latency and a
Figure 4. Comparison of n1 amplitude in 3 groups decrease in N2 amplitude from group1 to group3.

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 Int J Clin and Biomed Res. 2017;3(1): 13-17.
N2 AMPLITUDE
100
80
60
in nV
40
20
0
GROUP 1 GROUP 2 GROUP 3
N2 AMPLITUDE 90.38 31.04 13.98
Figure 8. Comparison of n2 amplitude in 3 groups
DISCUSSION
Various studies have been done on patient with diabetic
mellitus correlating the retinal function and potentials with
severity and duration of diabetes using Multifocal ERG
technique. Palmowski et al [10], in his study patients
underwent multifocal ERG testing reporting that implicit
times of Multifocal ERGs, averaged across the whole retina,
were significantly delayed in some diabetic eyes without
retinopathy. Whole field res ponse delays were greater in
magnitude and more prevalent among their group eyes with
NPDR. It was seen that in patients with NPDR, N1 latency was
delayed (mean=17.1ms), P1 latency (mean=32.3ms) and N1
amplitude was decreased (mean=19.9nV). In our study in
severe NPDR, the N1 latency was 17.33ms, P1 latency was
36.87ms and the N1 amplitude was 10.54nV. Similarly the P1
implicit time in this study was delayed (27.7ms) which was
found to be 28.59ms in our study in patients with mild to
moderate NPDR and further delayed to 34.11ms in severe
NPDR.
BRAD FORTUNE et al,[11] 1999, patients with non-proliferative
diabetic retinopathy (NPDR) and patients without
retinopathy compared with 16 age-matched, non-diabetic
subjects found that in eyes with NPDR, the implicit time of
responses was markedly delayed (e.g., up to 7 mSec from
normal).
The results demonstrated that Multifocal ERG[12] implicit time
analysis is highly sensitive method of assessment of local
retinal function in diabetics. The range of local ERG implicit
time observed for the normal eyes in this study was very
narrow, consistent with the findings of other Multifocal ERG
studies. Consequently, l ocal ERG delays as small as 2.5mSec
may be regarded as representing significant local retinal
dysfunction in diabetic eyes.
In eyes with NPDR, delays of local responses were greater
and were found throughout most of the retina than in eyes
without retinopathy. Response delays were progressively
worse towards the center of discrete ophthalmoscopic
lesions in the retinopathic eyes. Local ERGs delayed by 4
msec or longer were found only in, or immediately adjacent
to, diabetic retinal lesions. Local ERG amplitudes were more
Amruta Vijay More et al.,
Page 16
variable than implicit times - between normal eyes (10 times )
and within normal eyes (5 ti mes).
In our study the P1 implicit time was delayed by 11.48ms in
severe NPDR and by 5.96ms in mild-moderate NPDR as
compared to control. Similarly, the N1 latency delay was
more than 3ms, N2 and P1 latency delay was more than 7ms
as concluded by this study.
YING HAN ET AL,[13] 2004 concluded that the relative risk of
development of new retinopathy over 1 year in the areas
with abnormal baseline Multifocal erg implicit times was
approximately 21 times greater than that in the areas with
normal baseline Multifocal ergs. Mohamm.ad-sadegh
farahvash,[14] 2006, studied forty-one eyes with clinically
significant macular edema, tested and compared with 13 non
diabetic subjects and found that local electroretinogram
responses were significantly delayed and decreased in
amplitude in patients with clinically significant macular
edema.
CONCLUSION
Multifocal ERG is a useful indicator of diabetic retinopathy.
The significant delay in local responses provide a chance for
the detection and understanding of the various stages of
diabetic retinopathy.
The normal values of the various parameters of mfERG are
considered to be within a range rather than a discrete value.
In our study the mean of these values was calculated in the
control group with N1, P1 and N2 latency being 14.09ms,
29.76ms and 45.55ms, respectively. The N1, P1 and N2
amplitude was found to be 31.52nV, 73.61nV and 90.38nV,
respectively. The maximum delay in N1, P1 and N2 latency
was seen to be 3.24ms,7.11ms and 8.40ms respectively form
the normal value. We have also found a decrease in the
amplitude of the ERG waveform with the N1, P1 and N2
amplitude being 20.98 nv,61.48nV and 76.4 nV respectively
from the normal value. Also, it is helpful in cases with
clinically significant macular edema where the respons es a r e
remarkably delayed suggesting local retinal dysfunction and
macular pathology. It provides us information regarding the
condition of the macula and some idea about the extent of
ischemia affecting this area.
In conclusion, we can say that the delayed responses obtained
indicate abnormal retinal function corresponding to local
discrete retinopathic lesions. It provides a very sensitive and
objective assessment of the local retinal condition in various
stages of diabetic retinopathy.
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